Tuberculosis Strain Subverts Immune Response

ROBERT WILKINSON
Researchers may have glimpsed a means by which the tuberculosis bacterium could adapt itself to different human populations. The loss of a gene from one strain of tuberculosis (TB) allows the bug to subvert the immune response of its host, potentially explaining why the strain caused an unusually severe outbreak at a U.K. school, researchers report. Related strains are a major cause of the disease in India and among Asians living in the U.K., raising the possibility that the mutation could be part of an adaptation to those populations.

Despite being a scourge that kills more than two million people each year, Mycobacterium tuberculosis is believed to cause significant disease in only 5 to 10 percent of exposed individuals. Researchers were therefore curious about a well-documented 2001 outbreak at a community college in Leicester, U.K., in which 77 out of 254 who hosted the pathogen fell ill. Strains of tuberculosis vary widely in their genetic makeup, so researchers began looking for a genetic explanation of the high rate of disease. Investigators cultured the outbreak-causing strain of bacterium and found it lacked a gene called Rv1519 present in a reference strain.

At first blush the loss of the gene seems to make the outbreak strain less hardy, they found; it grew relatively slowly in a nutrient broth and was less tolerant to acidity and hydrogen peroxide than the reference bacterium. Interestingly, the outbreak strain grew at a normal pace in cultured human white blood cells, apparently by subverting the immune response to its benefit. The infected cells produce less inflammation-inducing chemicals--a major component of the immune response--and more anti-inflammatory chemicals, the group reports online October 2 in Proceedings of the National Academy of Sciences USA. The weakened immune response would explain the rate of disease seen in the Leicester TB outbreak.

Earlier this year researchers identified different subgroups of tuberculosis that coincide with specific ethnic populations, perhaps because they transmit best in those groups. The new study does not directly address the idea, says lead author Robert Wilkinson of Imperial College London and the University of Cape Town. "All we can say is it fits rather well with that scheme," he explains. Figuring out if circulating TB strains carry genetic variations that cause different disease outcomes is especially important for trying to design or administer a vaccine, says TB researcher Sebastien Gagneux of the Institute for Systems Biology. It's also a major challenge. "To get down to the real bacterial factors is really difficult," he says.